Competitive Renewal of the Yale SCOR on Women Health: Sex, Stress and Substance Abuse Substance use disorders (SUDs) are chronic relapsing illnesses with devastating psychosocial, health and societal consequences. Differential susceptibility to SUDs in men and women is well known. Historically, prevalence of disorders such as cocaine abuse is higher in men than women, but emerging evidence indicates that adolescent girls are as likely or slightly more likely to use and abuse substances, such as cocaine, than adolescent boys. Stress is a major factor increasing the vulnerability to develop SUDs in girls and in women. Our current SCOR findings indicate that females are more vulnerable to the addictive properties of abusive drugs and that stress markers such as early trauma and altered stress neurobiology plays a pivotal role in the continued drug use and relapse cycle in women. In this SCOR competitive renewal, we propose translational research that will systematically examine mechanisms of such increased vulnerability in girls and in women. Continued support is requested to conduct interdisciplinary studies to address the following three scientific goals: (1) to examine sex differences in the neural and psychobiological effects of prenatal cocaine exposure (PCE) on stress responses affecting risk of developing SUDs;(2) to evaluate the effects of sex-specific factors in the association between stress, drug seeking and vulnerability to cocaine relapse;and (3) to build scientific collaborations through consultation and research support so as to increase the study of sex-specific effects on stress and drug abuse among investigators locally, regionally and nationally. These goals will be accomplished by means of basic science and clinical studies conducted in animals and in humans. A greater understanding of these interactions will directly affect the development of sex-specific prevention and treatment approaches that will enhance the health of addicted women and their families. The following specific aims will be achieved by the SCOR: (1) To conduct a series of translational research projects on the interdisciplinary study of sex-specific effects in the association between stress and SUDs across the lifespan;(2) To extend the SCOR collaborative research program utilizing SCOR core scientific resources to facilitate the investigation of sex-specific factors in ongoing independently-funded research relating to the etiology, neurobiology and treatment of SUDs that includes faculty and research at other institutions;(3) To assist a range of young investigators from different disciplines both at Yale and at other institutions in conducting sex-specific research on stress and drug abuse through mentorship, research support and scientific consultation;(4) To establish inter-SCOR collaborations on common stress mechanisms to study similarities and differences in biological and social factors that contribute to stress-related disorders affecting women's health.